The role of solid-state form in determining the properties of Pharmaceuticals is a critical issue in drug delivery. The ability of a solid to exist as more than 1 polymorph, supramolecular isomers that differ only in packing and not constitution, creates a situation where each crystal form may have different bioavailability and stability. Only by discovering the presence of new polymorphs and their unique properties can the most efficacious form for a solid dosage be found. This proposal outlines a method for studying and controlling this important aspect of crystal growth. Specific Aim 1-Develop a general methodology for producing new polymorphs. We will create libraries of polymers that can heteronucleate crystallization of solids. It is proposed that varying the functional groups on the surface of the polymer and the orientation and density of these functional groups will allow kinetic access to new polymorphs by creating novel heteronucleation events. Specific Aim 2-lnvestigate the relationship between polymer structure and crystal polymorph obtained. Though it has been established that the majority of crystallizations on a macroscopic scale proceed through heteronucleation events, there is little information about the influence of the substrate on crystallization events. Using the approach developed in Specific Aim 1 to find polymers that create novel polymorphs, we will determine which characteristics are important for controlling polymorph production. Specific Aim 3-Determine the properties of novel polymorphs. With the ultimate goal of finding more efficacious forms of existing and new Pharmaceuticals, the determination of several key properties of the new polymorphs will be undertaken including stability, equilibrium solubility and dissolution rate. Brief description of public health relevance: The effectiveness of a drug substance is not solely related to its chemical composition but also to how the molecules arrange in the solid. This proposal offers a method for optimizing this important aspect of drug delivery and will lead to the development of more effective forms of current and future therapeutic agents. [unreadable] [unreadable] [unreadable]